Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series.
Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series.
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五名患者因 ETFDH 突变导致迟发性 MADD 的临床表现和遗传特征：病例系列
DOI：
10.3389/fneur.2021.747360
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发表时间：
2021
影响因子：
3.4
通讯作者：
Tang J
中科院分区：
文献类型：
--
作者：
Tang Z;Gao S;He M;Chen Q;Fang J;Luo Y;Yan W;Shi X;Huang H;Tang J
背景：晚发多酰基-COA脱氢酶缺乏症（LO-MADD）描述了由ETFDH突变引起的可治愈的常染色体隐性遗传疾病，导致ETF-偶联氧化还原酶的缺陷。几乎所有患者都对核黄素有反应。这项研究描述了五名LO-MADD患者的临床表现和遗传特征。
方法：从2018年到2021年，我们收集了五名在我们医院诊断患有LO-MADD的患者的临床和遗传数据，并回顾性地分析了其临床特征，实验室检查，肌电图，肌肉活检，遗传分析和结果数据。
结果：这项研究包括三名男性和两名女性，平均发作年龄为37.8岁。练习不耐受是最常见的表现。在所有患者中，血清肌酸激酶（CK）水平均显着升高，血浆酰基肉碱谱显示三种情况下长链酰基肉碱物种的增加。尿液有机酸研究显示，所有患者的羟基谷物酸水平高。电生理学证明了肌源性障碍。肌肉活检显示脂质储存肌病。分子分析在ETFDH中鉴定出了9个突变（三本小说和六个报道）。诊断后每天接受核黄素（100 mg）治疗的所有患者，运动不耐受和肌肉无力均大大改善。
结论：lo-madd是由ETFDH变体引起的，对核黄素的反应很好。确定了三种新型的ETFDH致病变异，扩大了中国人群的频谱，并促进了对ETFDH突变的未来解释和分析。
Background: Late-onset multiple acyl-CoA dehydrogenase deficiency (LO-MADD) describes a curable autosomal recessive genetic disease caused by ETFDH mutations that result in defects in ETF-ubiquinone oxidoreductase. Almost all patients are responsive to riboflavin. This study describes the clinical presentations and genetic characteristics of five LO-MADD patients. Methods: From 2018 to 2021, we collected clinical and genetic data on five patients diagnosed with LO-MADD at our hospital and retrospectively analyzed their clinical characteristics, laboratory examination, electromyography, muscle biopsy, genetic analysis, and outcome data. Results: This study included three males and two females with mean onset age of 37.8 years. Fluctuating exercise intolerance was the most common presentation. Serum creatine kinase (CK) levels were significantly elevated in all patients, and plasma acylcarnitine profiles revealed an increase in long-chain acylcarnitine species in three cases. The urinary organic acid study revealed a high level of hydroxyglutaric acid in all patients. Electrophysiology demonstrated myogenic impairment. Muscle biopsies revealed lipid storage myopathy. Molecular analysis identified nine mutations (three novels and six reported) in ETFDH. Exercise intolerance and muscle weakness were dramatically improved in all patients treated with riboflavin (100 mg) daily following diagnosis. Conclusions: LO-MADD is caused by ETFDH variants and responds well to riboflavin. Three novel ETFDH pathogenic variants were identified, expanding their spectrum in the Chinese population and facilitating future interpretation and analysis of ETFDH mutations.
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影响因子：
4.2
作者：
Haack, Tobias B.;Makowski, Christine;Yao, Yoshiaki;Graf, Elisabeth;Hempel, Maja;Wieland, Thomas;Tauer, Ulrike;Ahting, Uwe;Mayr, Johannes A.;Freisinger, Peter;Yoshimatsu, Hiroki;Inui, Ken;Strom, Tim M.;Meitinger, Thomas;Yonezawa, Atsushi;Prokisch, Holger
通讯作者：
Prokisch, Holger
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14.5
作者：
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通讯作者：
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4.2
作者：
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通讯作者：
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影响因子：
3.9
作者：
Ho, Gladys;Yonezawa, Atsushi;Christodoulou, John
通讯作者：
Christodoulou, John
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影响因子：
6.1
作者：
Liu, Xin-Yi;Wang, Zhi-Qiang;Wang, Ning
通讯作者：
Wang, Ning